Three YXXL Sequences of a Bovine Leukemia Virus Transmembrane Protein are Independently Required for Fusion Activity by Controlling Expression on the Cell Membrane

Viruses. 2019 Dec 10;11(12):1140. doi: 10.3390/v11121140.


Bovine leukemia virus (BLV), which is closely related to human T-cell leukemia viruses, is the causative agent of enzootic bovine leukosis, the most common neoplastic disease of cattle. The transmembrane subunit of the BLV envelope glycoprotein, gp30, contains three completely conserved YXXL sequences that fit an endocytic sorting motif. The two N-terminal YXXL sequences are reportedly critical for viral infection. However, their actual function in the viral life cycle remains undetermined. Here, we identified the novel roles of each YXXL sequence. Syncytia formation ability was upregulated by a single mutation of the tyrosine (Tyr) residue in any of the three YXXL sequences, indicating that each YXXL sequence is independently able to regulate the fusion event. The alteration resulted from significantly high expression of gp51 on the cell surface, thereby decreasing the amount of gp51 in early endosomes and further revealing that the three YXXL sequences are independently required for internalization of the envelope (Env) protein, following transport to the cell surface. Moreover, the 2nd and 3rd YXXL sequences contributed to Env protein incorporation into the virion by functionally distinct mechanisms. Our findings provide new insights regarding the three YXXL sequences toward the BLV viral life cycle and for developing new anti-BLV drugs.

Keywords: BLV; Env distribution; YXXL sequence; endosome; internalization; membrane binding; syncytia formation; virion incorporation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs*
  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cell Line
  • Cell Membrane / metabolism*
  • Cell Membrane / virology*
  • Cells, Cultured
  • Fluorescent Antibody Technique
  • Gene Expression
  • Host-Pathogen Interactions*
  • Humans
  • Leukemia Virus, Bovine / physiology*
  • Membrane Fusion*
  • Mutation
  • Protein Transport
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / metabolism*
  • Virus Attachment
  • Virus Release


  • Viral Envelope Proteins